Soft-tissue calcification occurs when calcium and other mineral salts are deposited in a tissue. Calcification of soft tissues plays a major role in the pathologies of a variety of diseases such as macular degeneration, cancer, kidney disease, and cardiovascular disease. In particular, arterial and valvular calcification promotes heart attacks and aortic valve stenosis, which represent major health problems and economic burden in the United States.
Cardiovascular calcification is a disease of dysregulated mineral metabolism, which leads to increased cardiovascular events and potentially death. Microcalcifications located in the thin fibrous cap overlying the necrotic core of atherosclerotic plaques may cause microfractures, which can lead to acute thrombosis and even sudden death due to fatal acute myocardial infarction (Huang H, Circulation, 2001; Virmani R, 2006; Vengrenyuk Y, 2006). Various therapeutic agents have been investigated to target cardiovascular calcification; these include statins (Aikawa E, Circulation, 2007; Monzack et al, 2009; Osman L, Circulation, 2006; Rajamannan N M, Circulation, 2005) and mineralocorticoid receptor antagonists (Gkizas S, Cardiovasc. Pharma, 2010; Jaffe I Z, ATVB, 2007), however as yet they have not proved beneficial in the clinical setting (Gilmanov D, Inter. Cardiovasc Thor Surg. 2010).
Accordingly, there is an unmet need in the art for new methods for the treatment of soft-tissue calcification including, but not limited to, cardiovascular calcification.